(1) Field of the Invention
The present invention relates generally to pharmaceutical lozenges and, more particularly, to a method for making a lozenge; the lozenge containing an antacid ingredient and an antiflatulent ingredient consisting of simethicone.
(2) Prior Art
Mitra, U.S. Pat. No. 4,163,777, discloses a lozenge containing antacid. The antacid in the lozenge is slowly dissolved in the mouth, which provides a sustained release of antacid which neutralizes stomach acid over a long period of time.
According to an official F.D.A. manuscript on over-the-counter drugs, simethicone is the only product that has been held to be a safe and effective antiflatulent. It has been widely used for years by itself or in combination with antacids in liquid and tablet form.
However, it has long been known that most antacids inactivate simethicone by adsorption (study of Morton Rezak published in the Journal of Pharmaceutical Science 55:538-539, May, 1966). Some of the antacids that have marked deleterious effects on the deforming activity of simethicone are aluminum hydroxide, magnesium carbonate, bismuth subcarbonate, magnesium carbonate-aluminum hydroxide coprecipitate, and others. The antacids that have the least effect are sodium bicarbonate and sodium citrate. Antacids with a medium effect are calcium carbonate, magnesium trisilicate and magnesium hydroxide.
Many attempts have been made in the past to overcome this incompatability of simethicone and antacids in the solid dosage form and patent literature on this subject for the period 1960 to 1980 is revealing. Primarily attempts have been, one way or another, to manufacture formulations where these two ingredients are physically kept apart.
The May U.S. Pat. No. 2,934,472 and Feinstone U.S. Pat. 2,951,011 respectively, pertain to antiflatulency of simethicone and combination of simethicone with antacid.
U.S. Pat. No. 3,382,150 issued to Grass and MacDonnell describes a process of spray-drying organopolysiloxanes with gums and various other materials that result in a free-flowing particulate material with the silicone coated with gums, etc. The purpose of this invention is to supply a convenient solid form of oily organopolysiloxane so that it can be easily incorporated in a tablet.
The Rider U.S. Pat. No. 3,422,185 describes the concept of activation of organopolysiloxanes by incorporation of small amounts of silica aerogel but does not address itself to the inactivation problem with antacids.
The Yen U.S. Pat. No. 3,501,571 discloses the art of dispersing the silicone first in an adsorbent such as lactose and then making the antacid tablet as a double-layered tablet where the antacid and simethicone are separated into different layers or are mixed and made into a single layer tablet.
The U.S. Pat. No. 3,767,794 issued to McVean and Tuereck teaches to disperse up to 20% simethicone in molten sorbitol and then incorporate the powdered, solidified simethicone into antacid tablets. The solidified sorbitol physically protects the simethicone from the antacid in a tablet and hence prevents its deactivation.
U.S. Pat. No. 4,127,650 of Buehler is similar to that of McVean and Tuereck except it uses a combination of glycerol and corn syrup.
Rider U.S. Pat. No. 4,198,390 proposes to achieve the same objective by incorporating the simethicone in a nonantacid layer and separating this from the antacid layer by a third layer which is termed the barrier layer.
Today, most commerical antacid-simethicone tablets are sold as two-layered products to prevent the inactivation of simethicone in the tablet form by antacids. The first layer contains only simethicone and diluents and the second layer contains antacids and diluents but with no simethicone. The purpose of manufacturing the product in two layers is to prevent the inactivation of simethicone by the antacids through intimate contact.
However, these commercial products are not entirely successful in preventing inactivation of simethicone.
Most of the antacid-simethicone tablets currently available in the marketplace in the United States, have been tested by the inventor and found to have not only the simethicone partially deactivated but, in most cases, completely deactivated in the available products. Thus, most of these antacids did not pass the USP XX defoaming test for simethicone. Only a few of of these products, on some occasions, barely passed the test; and it can be surmised that with more shelf life these products would also fail the test.
Furthermore, at least a partial explanation of deactivation was unexpectedly discovered. While assaying the two layers of commercial products, it was discovered that approximately 90 percent of the labeled amount of simethicone was in the antacid layer and only 10 percent of the labeled amount of simethicone was in the nonantacid layer. This fact could only be explained by assuming that after the tablet was manufactured, the simethicone migrated from the antacid-free simethicone layer to the antacid layer due to the strong attractive force on the simethicone by the antacid. While it has been observed before that commercial antacid-simethicone tablets fail to pass the USP deforming test, an adequate explanation of the phenomenon was lacking.
It would be desirable to have a commercially-acceptable product which combines antacid and simethicone in one layer and which has a sustained release of both products. In the lozenge of the invention, the antacid and the simethicone are in the same layer without any deactivation of the simethicone. This lack of deactivation of simethicone, while in intimate contact with antacid, lacks an adequate explanation at this time. Studies show that in the lozenge of the present invention there is no diminution of simethicone activity even at elevated temperatures with passage of time.